Targeting Mitochondria in Alzheimer Disease: Rationale and Perspectives

Chiara Lanzillotta, Fabio Di Domenico, Marzia Perluigi, D. Allan Butterfield

Research output: Contribution to journalReview articlepeer-review

27 Scopus citations

Abstract

A decline in mitochondrial function plays a key role in the aging process and increases the incidence of age-related disorders, including Alzheimer disease (AD). Mitochondria—the power station of the organism—can affect several different cellular activities, including abnormal cellular energy generation, response to toxic insults, regulation of metabolism, and execution of cell death. In AD subjects, mitochondria are characterized by impaired function such as lowered oxidative phosphorylation, decreased adenosine triphosphate production, significant increased reactive oxygen species generation, and compromised antioxidant defense. The current review discusses the most relevant mitochondrial defects that are considered to play a significant role in AD and that may offer promising therapeutic targets for the treatment/prevention of AD. In addition, we discuss mechanisms of action and translational potential of some promising mitochondrial and bioenergetic therapeutics for AD including compounds able to potentiate energy production, antioxidants to scavenge reactive oxygen species and reduce oxidative damage, glucose metabolism, and candidates that target mitophagy. While mitochondrial therapeutic strategies have shown promise at the preclinical stage, there has been little progress in clinical trials. Thus, there is an urgent need to better understand the mechanisms regulating mitochondrial homeostasis in order to identify powerful drug candidates that target ‘in and out’ the mitochondria to preserve cognitive functions.

Original languageEnglish
Pages (from-to)957-969
Number of pages13
JournalCNS Drugs
Volume33
Issue number10
DOIs
StatePublished - Oct 1 2019

Bibliographical note

Funding Information:
This work was supported in part by NIH Grants to DAB [AG060056; AG055596-01A1].

Publisher Copyright:
© 2019, Springer Nature Switzerland AG.

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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